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KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for Prostate- Specific Antigen-Relapse Following Radical Prostatectomy  Johannes Stein,

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Presentation on theme: "KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for Prostate- Specific Antigen-Relapse Following Radical Prostatectomy  Johannes Stein,"— Presentation transcript:

1 KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for Prostate- Specific Antigen-Relapse Following Radical Prostatectomy  Johannes Stein, Michael Majores, Magdalena Rohde, Soyoung Lim, Simon Schneider, Eliana Krappe, Jörg Ellinger, Manfred Dietel, Carsten Stephan, Klaus Jung, Sven Perner, Glen Kristiansen, Jutta Kirfel  The American Journal of Pathology  Volume 184, Issue 9, Pages (September 2014) DOI: /j.ajpath Copyright © 2014 American Society for Investigative Pathology Terms and Conditions

2 Figure 1 Immunohistochemical staining of KDM5C in PCa. A: Despite frequently detectable cytoplasmic staining of weak or moderate intensity, an additional nuclear staining could be distinguished in a subset of tumors. C: In contrast, other samples only showed an exclusively cytoplasmic (with negative nuclei) staining. Inset in A shows immunohistochemical staining of KDM5C in benign tissue. Bar graphs show the distributions of nuclear (B) and cytoplasmic (D) stainings of the tumors of the cohorts. The American Journal of Pathology  , DOI: ( /j.ajpath ) Copyright © 2014 American Society for Investigative Pathology Terms and Conditions

3 Figure 2 A: Kaplan-Meier survival analysis. Kaplan-Meier analysis of 761 prostate tumors shows that nuclear KDM5C expression is associated with shorter survival of patients with PCa. Kaplan-Meier analysis comparing PFS of nuclear KDM5C stratified according to the Gleason groups 7 (B), <7 (C), and >7 (D). In this model the prognostic effect is most pronounced for the Gleason group 7 (group 7, P < 0.001; group < 7, P = 0.273; group > 7, P = 0.308). n = 367 (B), n = 264 (C), and n = 130 (D). P < 0.001 (A). The American Journal of Pathology  , DOI: ( /j.ajpath ) Copyright © 2014 American Society for Investigative Pathology Terms and Conditions

4 Figure 3 Inhibition of KDM5C impairs PCa growth in vitro. A: Confirmation of differential expression of KDM5C in prostate cell lines by using real-time PCR analysis. B: qPCR analysis to determine the knockdown of LSD1 mRNA in PC3 cells 6 days after transfection. C: MTT assay of PC3 cells treated with two different siRNAs against KDM5C detects a significant reduction in cell number after 6 days of incubation. D: Knockdown of KDM5C induces down-regulation of proliferation-associated genes such as MKI67 and PCNA and induction of p21. qPCR analysis was done in PC3 cells with two siRNAs directed against KDM5C or with scrambled control siRNA. In all experiments, 18S rRNA was used as the endogenous reference gene. Data are expressed as fold change to scrambled siRNA transfected samples which were set to 1 (B–D). ∗P < 0.05. The American Journal of Pathology  , DOI: ( /j.ajpath ) Copyright © 2014 American Society for Investigative Pathology Terms and Conditions


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